Induction of penile erection by intracavernosal and transurethral administration of novel nitric oxide donors in the cat

被引:21
作者
Champion, HC
Bivalacqua, TJ
Wang, R
Kadowitz, PJ
Keefer, LK
Saavedra, JE
Hrabie, JA
Doherty, PC
Hellstrom, WJG
机构
[1] Tulane Univ, Sch Med, Dept Urol SL42, New Orleans, LA 70112 USA
[2] Tulane Univ, Sch Med, Dept Pharmacol, New Orleans, LA 70112 USA
[3] NCI, Comparat Carcinogenesis Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA
[4] NCI, SAIC Fredrick, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA
[5] VIVUS Inc, Mt View, CA USA
关键词
penile erection; novel nitric oxide donors; diazeniumdiolates; transurethral; intracavernosal;
D O I
10.1016/S0022-5347(05)68875-1
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Purpose: The effects of novel nitric oxide (NO) donors administered intracavernosally and transurethrally on erectile function in the anesthetized cat were evaluated. Materials and Methods: In pentobarbital-anesthetized cats, increases in intracavernosal pressure, penile length, and duration of erectile response were determined after intracavernosal and transurethral injections of novel NO donors (MAHMA/NO, PAPA/NO, DEA/NO, PIPERAZI/NO and PROLI/NO). All parameters were measured after administration of NO donors intracavernosally via a 30-gauge needle and urethrally via a Jelco i.v. catheter in a volume of 200 mu l. Systemic arterial pressure was also assessed in these experiments. All NO donors were compared with a triple-drug control combination comprised of papaverine (1.65 mg.), prostaglandin E-1 (0.5 mu g.), and phentolamine (25 mu g.). Results: MAHMA/NO, PAPA/NO, DEA/NO, PIPERAZI/NO and PROLI/NO induced dose dependent increases in intracavernosal pressure and penile length (p <0.05) when administered intracavernosally. The increases in cavernosal pressure and penile length were comparable to those observed with the triple-drug control combination. The maximum increase in cavernosal pressure in response to PROLI/NO and PAPA/NO was associated with no significant change in systemic arterial pressure. Transurethral administration of PROLI/NO and PIPERAZI/NO induced dose-dependent increases in cavernosal pressure and penile length (p <0.05). The response was similar to that of the triple-drug control combination, except that transurethral PROLI/NO and PIPERAZI/NO had no significant effect on systemic blood pressure. Conclusions: NO donors caused dose-dependent increases in cavernosal pressure when administered intracavernosally and transurethrally. These data suggest further exploration of the use of NO donors for the treatment of erectile dysfunction.
引用
收藏
页码:2013 / 2019
页数:7
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